Studies in a normal rat model were undertaken with 3H and 14C isotopes of 2-deoxyglucose (2DG) as a model anticancer agent to illustrate pharmacologic principles of the intra-arterial drug delivery advantage. In particular, the regional target tissue was defined as the right brain cortex and the regional artery the right common carotid artery. First, this model illustrates that the first pass delivery advantage to the target tissue (right brain cortex) exists for only a short time following arterial (intra-carotid) infusion. No advantage could be demonstrated subsequently. Second, the model illustrates that the intra-arterial advantage approaches the model's physiologic limits based on carotid blood flow and cardiac output. Third, tissue analysis demonstrates that there is increased delivery of drug to the target tissue (regional delivery advantage), and that less drug is delivered to other systemic organs (systemic protection advantage). Last, the model illustrates that the delivery advantage which would be predicted on the basis of the pharmacokinetic behavior of the model drug, 2DG, can be directly confirmed in the laboratory.